Industry Payments to Cardiology Fellows and Early-Career Cardiologists.

This cohort study evaluates marketing payments from pharmaceutical and medical device manufacturers to physician trainees before and after fellowship graduation.

Funding of evidence included within public comments submitted to inform Medicare national coverage determinations.

The Centers for Medicare & Medicaid Services (CMS) relies on public comments submitted in response to proposed national coverage determinations to assist the agency in determining the coverage of items and services for Medicare beneficiaries. In a cross-sectional study, we characterized the cited evidence and what funding supported the cited evidence submitted in public comments to CMS for all therapeutic medical device national coverage determinations finalized between June 2019 and June 2022. Of 681 public comments, 159 (23%) cited at least 1 identifiable published scientific journal article. Within these 159 public comments, 198 unique articles were cited, 170 (86%) of which included funding statements or author disclosures. Among these, 96 (56%) disclosed funding from manufacturers that would benefit from Medicare coverage and/or were written by author(s) who received funding from these manufacturers. In summary, most public commenters for national coverage determinations did not cite published scientific journal articles to support their positions. Among those who did, more than half of articles were directly funded by manufacturers that would benefit from coverage. Greater funding of independent, non-industry-supported research may help provide unbiased evaluations of benefits and harms to support Medicare coverage decisions.

Medicare Coverage and Patient Out-of-Pocket Costs for Cardiovascular-Kidney-Metabolic Medications.

This cross-sectional study evaluates the association between Medicare coverage and patient out-of-pocket costs for cardiovascular-kidney-metabolic medications.

Blood Pressure Control and Maintenance in a Prospective Cohort of Younger Veterans: Roles of Sex, Race, Ethnicity, and Social Determinants of Health.

Background: Proactive blood pressure (BP) management is particularly beneficial for younger Veterans, who have a greater prevalence and earlier onset of cardiovascular disease than non-Veterans. It is unknown what proportion of younger Veterans achieve and maintain BP control after hypertension onset and if BP control differs by demographics and social deprivation. Methods: Electronic health records were merged from Veterans who enrolled in VA care 10/1/2001-9/30/2017 and met criteria for hypertension - first diagnosis or antihypertensive fill. BP control (140/90 mmHg), was estimated 1, 2, and 5 years post-hypertension documentation, and characterized by sex, race, and ethnicity. Adjusted logistic regressions assessed likelihood of BP control by these demographics and with the Social Deprivation Index (SDI). Results: Overall, 17% patients met criteria for hypertension (n=198,367; 11% of women, median age 41). One year later, 59% of men and 65% of women achieved BP control. After adjustment, women had a 72% greater odds of BP control than men, with minimal change over 5 years. Black adults had a 22% lower odds of BP control than White adults. SDI did not significantly change these results. Conclusions: In the largest study of hypertension in younger Veterans, 41% of men and 35% of women did not have BP control after 1 year, and BP control was consistently better for women through 5 years. Thus, the first year of hypertension management portends future, long-term BP control. As social deprivation did not affect BP control, the VA system may protect against disadvantages observed in the general U.S. population.

Reporting of Demographics & Subgroup Analyses in Premarketing Studies of FDA Approved High-Risk Cardiovascular Devices, 2014-2022.

Background: Representation of diverse study populations in pivotal clinical trials for medical devices and subgroup analyses for demographic groups to explore differences in safety and effectiveness are essential to understanding the benefits and risks in diverse populations. The US Food and Drug Administration (FDA) has taken many steps to improve transparency and subgroup analyses over the past decade, but there has not been a recent evaluation of demographic reporting and subgroup analyses. Methods: We reviewed all FDA Premarket Approvals for high-risk cardiovascular devices from 2014 to 2022, focusing on pivotal studies supporting device approval. We abstracted detailed demographic data about the age, sex, race, ethnicity, and socioeconomic position of study participants. We also assessed the presence and results of subgroup analyses to understand the safety and effectiveness of devices across trial populations. Results: Analysis of 92 pivotal studies revealed that age and sex were reported in 96.7% of the studies, while race and ethnicity were reported in 71.7% and 58.7%, respectively. However, only 7.9% of studies explicitly detailed the participation of older adults (≥65 years) and no studies reported patients' socioeconomic position. Subgroup analyses by sex were conducted in 70.7% of studies, with 12.3% reporting significant differences. In contrast, analyses by race and ethnicity were performed in only 12.0% of the studies, with 9.1% reporting significant differences. Conclusion: Approximately one-third of pivotal studies for high-risk cardiovascular devices approved by the FDA from 2014 to 2022 did not report the race of study participants, nearly 40% did not report ethnicity, and more than 90% did not report the participation of older adults (≥65 years). Subgroup analyses were infrequently conducted by age or race and ethnicity. There is a need for better trial demographic reporting and conduct of subgroup analyses in premarketing studies to ensure the safety and effectiveness of medical devices for all patients.

Effectiveness, utilisation and cost associated with implantable loop recorders versus external monitors after ischaemic or cryptogenic stroke.

OBJECTIVE: Implantable loop recorders (ILRs) are increasingly used for long-term rhythm monitoring after ischaemic and cryptogenic stroke, with the goal of detecting atrial fibrillation (AF) and subsequent initiation of oral anticoagulation to reduce risk of adverse clinical outcomes. There is a need to determine the effectiveness of different rhythm monitoring strategies in this context. METHODS: We conducted a retrospective cohort analysis of individuals with commercial and Medicare Advantage insurance in Optum Labs Data Warehouse who had incident ischaemic or cryptogenic stroke and no prior cardiovascular implantable electronic device from 1 January 2016 to 30 June 2021. Patients were stratified by rhythm monitoring strategy: ILR, long-term continuous external cardiac monitor (>48 hours to 30 days) or Holter monitor (≤48 hours). The primary outcome was risk-adjusted all-cause mortality at 12 months. Secondary outcomes included new diagnosis of AF and oral anticoagulation, bleeding, and costs. RESULTS: Among 48 901 patients with ischaemic or cryptogenic stroke, 9235 received an ILR, 29 103 long-term continuous external monitor and 10 563 Holter monitor only. Mean age was 69.9 (SD 11.9) years and 53.5% were female. During the 12-month follow-up period, patients who received ILRs compared with those who received long-term continuous external monitors had a higher odds of new diagnosis of AF and oral anticoagulant initiation (adjusted OR 2.27, 95% CI 2.09 to 2.48). Compared with patients who received long-term continuous external monitors, those who received ILRs had similar 12-month mortality (HR 1.00; 95% CI 0.89 to 1.12), with approximately $13 000 higher costs at baseline (including monitor cost) and $2500 higher costs during 12-month follow-up. CONCLUSIONS: In this large real-world study of patients with ischaemic or cryptogenic stroke, ILR placement resulted in more diagnosis of AF and initiation of oral anticoagulation, but no difference in mortality compared with long-term continuous external monitors.

Prices and complications in hospital-based and freestanding surgery centers.

OBJECTIVES: To quantify differences in prices paid and procedural complications incurred in hospital outpatient departments (HOPDs) and freestanding ambulatory surgery centers (ASCs). STUDY DESIGN: Observational study using deidentified 2019-2020 insurance claims from Blue Cross Blue Shield insurance plans nationally, with information on prices paid and complications incurred for colonoscopy, knee or shoulder arthroscopy, and cataract removal surgery. METHODS: The data include 1,662,183 patients who received a colonoscopy, 53.5% of whom were treated in HOPDs; 259,200 patients who underwent arthroscopy, 61.0% of whom were treated in HOPDs; and 173,664 patients who had cataract removal surgery, 34.7% of whom were treated in HOPDs. Multivariable linear regression methods were used to identify the associations between HOPD and ASC site of care, prices, and complications after adjusting for patient demographics, risk, and geographic market location. RESULTS: After adjusting for patient characteristics, risk, and geographic market location, prices paid in HOPDs were 54.9% higher than those charged in ASCs for colonoscopy (95% CI, 53.6%-56.1%), 44.4% higher for arthroscopy (95% CI, 43.0%-45.8%), and 44.0% higher for cataract removal surgery (95% CI, 42.9%-45.5%). Adjusted rates of complications were slightly higher in HOPDs than ASCs for colonoscopy over a 90-day interval but similar over the 7- and 30-day intervals. Rates were statistically and clinically similar between the 2 sites of care for arthroscopy and cataract removal. CONCLUSIONS: The higher prices charged in HOPDs for the 3 ambulatory procedures were not balanced by better quality-as measured by rates of procedural complications-compared with procedures performed in nonhospital ASCs.

Intravascular Microaxial Left Ventricular Assist Device Manufacturer Payments to Cardiologists and Use of Devices.

This study examines whether payments from a left ventricular assist device manufacturer to cardiologists performing percutaneous coronary intervention were associated with any use of the devices.

Informational letters or postcards to initiate remote monitoring among veterans with pacemakers and implantable cardioverter-defibrillators: A randomized, controlled trial.

BACKGROUND: Remote monitoring (RM) of pacemakers and implantable cardioverter-defibrillators (ICDs) is a Class 1, Level of Evidence A recommendation because of its multitude of clinical benefits. However, RM adherence rates are suboptimal, precluding patients from achieving these benefits. There is a need for direct-to-patient efforts to improve adherence. METHODS: In this national randomized, controlled trial conducted in the Veterans Health Administration (VHA), 2120 patients with a pacemaker or ICD who had not sent an RM transmission for ≥1 year (and usually ≥3 years) while under VHA care for their device were randomly assigned to be mailed a postcard (n = 1076) or a detailed letter (n = 1044). The postcard described what RM does and its key benefits (reduced mortality and fewer in-person visits). The letter provided a similar message but included more details about RM benefits and the process. The primary outcome was an RM transmission sent within 90 days of mailing, and a secondary outcome was an RM transmission sent within 365 days. RESULTS: The primary outcome was achieved in 121 (11.3%) in the postcard and 96 patients (9.2%) in the letter group (p = .12). The secondary outcome was achieved in 266 (24.7%) and 239 (22.9%), respectively (p = .32). CONCLUSIONS: This randomized trial showed no significant difference in the proportion of chronically non-adherent patients who sent an RM transmission after receiving a low-cost postcard or a detailed, higher-cost letter encouraging their participation in RM. However, as only a minority of patients responded to either, further work is needed to engage patients in the life-saving benefits of RM.

Use of Electronic Health Records to Characterize Patients with Uncontrolled Hypertension in Two Large Health System Networks.

Background: Improving hypertension control is a public health priority. However, consistent identification of uncontrolled hypertension using computable definitions in electronic health records (EHR) across health systems remains uncertain. Methods: In this retrospective cohort study, we applied two computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥ 18 years) with hypertension receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single blood pressure (BP) measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). Results: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p < 0.001; 49.7% versus 41.2% in OneFlorida; p < 0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p = 0.04; 42.2% versus 34.8% in OneFlorida; p < 0.001). Patients with controlled and uncontrolled hypertension had similar rates of short-term (at 3 and 6 months) and long-term (at 12 and 24 months) clinical outcomes. The two computable definitions generated consistent results. Conclusions: Our findings illustrate the potential of leveraging EHR data, employing computable definitions, to conduct effective digital population surveillance in the realm of hypertension management.

Monitoring of Remotely Reprogrammable Implantable Loop Recorders With Algorithms to Reduce False-Positive Alerts.

BACKGROUND: Implantable loop recorders (ILRs) are increasingly placed for arrhythmia detection. However, historically, ≈75% of ILR alerts are false positives, requiring significant time and effort for adjudication. The LINQII and LUX-Dx are remotely reprogrammable ILRs with dual-stage algorithms using artificial intelligence to reduce false positives, but their utility in routine clinical practice has not been studied. METHODS AND RESULTS: We identified patients with the LINQII and LUX-Dx who were monitored by the Veterans Affairs National Cardiac Device Surveillance Program between March and June 2022. ILR programming was customized on the basis of implant indication. All alerts and every 90-day scheduled transmissions were manually reviewed. ILRs were remotely reprogrammed, as appropriate, after false-positive alerts or 2 consecutive same-type alerts, unless there was ongoing clinical need for that alert. Outcomes were total number of transmissions and false positives. We performed medical record review to determine if patients experienced any adverse clinical events, including hospitalization and mortality. Among 117 LINQII patients, there were 239 total alerts, 43 (18.0%) of which were false positives. Among 105 LUX-Dx patients, there were 300 total alerts, 115 (38.3%) of which were false positives. LINQIIs were reprogrammed 22 times, resulting in a decrease in median alerts/day from 0.13 to 0.03. LUX-Dx ILRs were reprogrammed 52 times, resulting in a decrease from 0.15 to 0.01 median alerts/day. There were no adverse clinical events that could have been identified by superior or earlier arrhythmia detection. CONCLUSIONS: ILRs with artificial intelligence algorithms and remote reprogramming ability are associated with reduced alert burden because of higher true-positive rates than prior ILRs, without missing potentially consequential arrhythmias.

Hospital Prices for Physician-Administered Drugs for Patients with Private Insurance.

BACKGROUND: Hospitals can leverage their position between the ultimate buyers and sellers of drugs to retain a substantial share of insurer pharmaceutical expenditures. METHODS: In this study, we used 2020-2021 national Blue Cross Blue Shield claims data regarding patients in the United States who had drug-infusion visits for oncologic conditions, inflammatory conditions, or blood-cell deficiency disorders. Markups of the reimbursement prices were measured in terms of amounts paid by Blue Cross Blue Shield plans to hospitals and physician practices relative to the amounts paid by these providers to drug manufacturers. Acquisition-price reductions in hospital payments to drug manufacturers were measured in terms of discounts under the federal 340B Drug Pricing Program. We estimated the percentage of Blue Cross Blue Shield drug spending that was received by drug manufacturers and the percentage retained by provider organizations. RESULTS: The study included 404,443 patients in the United States who had 4,727,189 drug-infusion visits. The median price markup (defined as the ratio of the reimbursement price to the acquisition price) for hospitals eligible for 340B discounts was 3.08 (interquartile range, 1.87 to 6.38). After adjustment for drug, patient, and geographic factors, price markups at hospitals eligible for 340B discounts were 6.59 times (95% confidence interval [CI], 6.02 to 7.16) as high as those in independent physician practices, and price markups at noneligible hospitals were 4.34 times (95% CI, 3.77 to 4.90) as high as those in physician practices. Hospitals eligible for 340B discounts retained 64.3% of insurer drug expenditures, whereas hospitals not eligible for 340B discounts retained 44.8% and independent physician practices retained 19.1%. CONCLUSIONS: This study showed that hospitals imposed large price markups and retained a substantial share of total insurer spending on physician-administered drugs for patients with private insurance. The effects were especially large for hospitals eligible for discounts under the federal 340B Drug Pricing Program on acquisition costs paid to manufacturers. (Funded by Arnold Ventures and the National Institute for Health Care Management.).

Physicians' Perspectives On FDA Regulation Of Drugs And Medical Devices: A National Survey.

Physicians' knowledge of Food and Drug Administration (FDA) approval processes is important in informing clinical decisions and patient discussions. Among a randomly selected national sample of 509 internists, cardiologists, and oncologists, 41 percent reported moderate or better understanding of the FDA's drug approval process, and 17 percent reported moderate or better understanding of the FDA's medical device approval process. Nearly all physicians thought that randomized, blinded trials that met primary endpoints should be very important factors required to secure regulatory approval. Also, nearly all physicians thought that the FDA should revoke approval for accelerated-approval drugs or breakthrough devices that did not show benefit in postapproval studies. Our findings suggest that physicians commonly lack familiarity with drug and medical device regulatory practices and are under the impression that the data supporting FDA drug and high-risk device approvals are more rigorous than they often are. Physicians would value more rigorous premarket evidence, as well as regulatory action for drugs and devices that do not demonstrate safety and effectiveness in the postmarket setting.

Informational Postcards Increase Engagement with Remote Monitoring Among Veterans with Pacemakers and Implantable Cardioverter-Defibrillators: a Stepped-Wedge Randomized Controlled Trial.

BACKGROUND: Remote monitoring (RM) of pacemakers and implantable cardioverter-defibrillators (ICDs) reduces morbidity and mortality. However, many patients are not adherent to RM. OBJECTIVE: To test the effect of informational postcards on RM adherence. DESIGN/PATIENTS: Stepped-wedge randomized controlled trial among Veterans with pacemakers and ICDs. INTERVENTION: In wave 1, Veterans who had sent at least 1 transmission within the past 2 years but had become non-adherent were randomly assigned to receive a postcard or no postcard. Those receiving postcards were randomized to 1 of 2 messages: (1) a"warning" postcard describing risks of non-adherence or (2) an "encouraging" postcard describing benefits of adherence. In wave 2, Veterans who had either not received a postcard in wave 1 or had since become non-adherent were mailed a postcard (again, randomized to 1 of 2 messages). Patients who did not send an RM transmission within 1 month were mailed a second, identical postcard. MAIN MEASURES: Transmission within 70 days. KEY RESULTS: Overall, 6351 Veterans were included. In waves 1 and 2, postcards were mailed to 5657 Veterans (2821 "warning" messages and 2836 "encouraging" messages). Wave 1 included 2178 Veterans as controls (i.e., not mailed a postcard), some of whom received a postcard in wave 2 if they remained non-adherent. In wave 2, 3473 postcards were sent. Of the 5657 patients mailed a postcard, 2756 (48.7%) sent an RM transmission within 70 days, compared to 530 (24.3%) of 2178 controls (absolute difference 24.4%, 95% confidence interval [CI] 22.2%, 26.6%). Of those who sent a transmission, 71.8% did so after the first postcard. Transmission rates at 70 days did not significantly differ between "warning" and "encouraging" messages (odds ratio 1.04, 95% CI 0.92, 1.18). CONCLUSIONS: Informational postcards led to a 24.4% absolute increase in adherence at 70 days among Veterans with pacemakers and ICDs who were non-adherent to RM.

Clinical Phenotyping with an Outcomes-driven Mixture of Experts for Patient Matching and Risk Estimation.

Observational medical data present unique opportunities for analysis of medical outcomes and treatment decision making. However, because these datasets do not contain the strict pairing of randomized control trials, matching techniques are to draw comparisons among patients. A key limitation to such techniques is verification that the variables used to model treatment decision making are also relevant in identifying the risk of major adverse events. This article explores a deep mixture of experts approach to jointly learn how to match patients and model the risk of major adverse events in patients. Although trained with information regarding treatment and outcomes, after training, the proposed model is decomposable into a network that clusters patients into phenotypes from information available before treatment. This model is validated on a dataset of patients with acute myocardial infarction complicated by cardiogenic shock. The mixture of experts approach can predict the outcome of mortality with an area under the receiver operating characteristic curve of 0.85 ± 0.01 while jointly discovering five potential phenotypes of interest. The technique and interpretation allow for identifying clinically relevant phenotypes that may be used both for outcomes modeling as well as potentially evaluating individualized treatment effects.